Effect of mechanical denaturation on surface free energy of protein powders.

Globular proteins are important both as therapeutic agents and excipients. However, their fragile native conformations can be denatured during pharmaceutical processing, which leads to modification of the surface energy of their powders and hence their performance. Lyophilized powders of hen egg-white lysozyme and β-galactosidase from Aspergillus oryzae were used as models to study the effects of mechanical denaturation on the surface energies of basic and acidic protein powders, respectively.

Equation to Line the Borders of the Folding-Unfolding Transition Diagram of Lysozyme.

It is important for the formulators of biopharmaceuticals to predict the folding-unfolding transition of proteins. This enables them to process proteins under predetermined conditions, without denaturation. Depending on the apparent denaturation temperature (Tm) of lysozyme, we have derived an equation describing its folding-unfolding transition diagram.

Mapping the solid-state properties of crystalline lysozyme during pharmaceutical unit-operations.

Bulk crystallisation of protein therapeutic molecules towards their controlled drug delivery is of interest to the biopharmaceutical industry. The complexity of biotherapeutic molecules is likely to lead to complex material properties of crystals in the solid state and to complex transitions. This complexity is explored using batch crystallised lysozyme as a model.

Effect of formulation parameters and drug-polymer interactions on drug release from starch acetate matrix tablets.

The aim of this study was to determine, whether interactions between a drug and hydrophobic polymer matrix are present, and if so, how they affect the drug release. In addition, the most important formulation parameters, for example porosity or structure of the tablet, which have the greatest impact on drug release, were defined. Six different drug compounds, that is allopurinol, acyclovir, metronidazole, paracetamol, salicylamide and theophylline, were used in different formulations with hydrophobic starch acetate (DS 2.

The impact of low-level inorganic impurities on key physicochemical properties of paracetamol.

Trace inorganic impurities in active pharmaceutical ingredients (APIs) while having limited toxicological significance might affect the down stream processing properties of those substances. The level of impurities in paracetamol batches was quantified and mapped using inductively coupled polarization mass spectrometry (ICP-MS) and scanning electron microscopy coupled with energy dispersive X-ray microanalysis (SEM-EDX). The physical form of samples was assessed using X-ray powder diffraction (XRPD) and characterised thermally using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA).

Polymer-mediated disruption of drug crystallinity.

Ibuprofen (IB), a BCS Class II compound, is a highly crystalline substance with poor solubility properties. Here we report on the disruption of this crystalline structure upon intimate contact with the polymeric carrier cross-linked polyvinylpyrrolidone (PVP-CL) facilitated by low energy simple mixing. Whilst strong molecular interactions between APIs and carriers within delivery systems would be expected on melting or through solvent depositions, this is not the case with less energetic mixing.

Design and evaluation of celecoxib porous particles using melt sonocrystallization.

Purpose: The purpose of the article was to study melt sonocrystallization (MSC) for a drug forming a viscous melt when processed below its glass transition temperature.

Methods: A molten mass of drug was poured in a vessel containing deionized water, maintained at 40 degrees C using cryostatic bath, and sonicated for 1 min using probe ultrasonicator at an amplitude of 80% and a cycle of 0.8 per second.

Development of a robust procedure for assessing powder flow using a commercial avalanche testing instrument.

The objectives of this work were to develop a robust procedure for assessing powder flow using a commercial avalanche testing instrument and to define the limits of its performance. To achieve this a series of powdered pharmaceutical excipients with a wide range of flow properties was characterized using such an instrument (Aeroflow, TSI Inc., St.

Quantitative analysis of mannitol polymorphs. X-ray powder diffractometry--exploring preferred orientation effects.

Mannitol is a polymorphic parmaceutical excipient, which commonly exists in three forms: alpha, beta and delta. Each polymorph has a needle-like morphology, which can give preferred orientation effects when analysed by X-ray powder diffractometry (XRPD) thus providing difficulties for quantitative XRPD assessments. The occurrence of preferred orientation may be demonstrated by sample rotation and the consequent effects on X-ray data can be minimised by reducing the particle size.

Quantitative analysis of mannitol polymorphs. FT-Raman spectroscopy.

Mannitol is a polymorphic excipient which is usually used in pharmaceutical products as the beta form, although other polymorphs (alpha and delta) are common contaminants. Binary mixtures containing beta and delta mannitol were prepared to quantify the concentration of the beta form using FT-Raman spectroscopy. Spectral regions characteristic of each form were selected and peak intensity ratios of beta peaks to delta peaks were calculated.

Analysis of the surface energy of pharmaceutical powders by inverse gas chromatography.

The behavior of pharmaceutical solids, during either processing or use, can be noticeably affected by the surface energetics of the constituent particles. Several techniques exist to measure the surface energy, for example, sessile drop, and dynamic contact angle measurements. Inverse gas chromatography (IGC) is an alternative technique where the powder surface is characterized by the retention behavior of minute quantities of well-characterized vapors that are injected into a column containing the material of interest.